Effects of TUDCA on Endothelial Function in Type 2 DM

Pilot Study of The Effects of Tauroursodeoxycholic Acid (TUDCA) on Endothelial Function in Subjects With Type 2 Diabetes Mellitus

The pilot study is designed to investigate the acute and chronic effects of the diet supplement tauroursodeoxycholic acid (TUDCA) on endothelial function in participants with type 2 diabetes mellitus.

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus, Type 2; Endothelial Dysfunction; Insulin Response
• Intervention / Treatment: Dietary supplement: Tauroursodeoxycholic acid

Detailed Description

This is a pilot study designed to investigate the effect of two doses of TUDCA on endothelial function.All subjects will receive 500 mg/day in a one week run-in period and then 1750 mg/day in one week treatment period. The study will consist of four visits (screening visit and three study visits), and last up to 2 weeks for individual subjects, depending on the time between visits. It is estimated that the study will last two years from IRB approval through data analysis.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 2 diabetes mellitus defined as fasting glucose greater than or equal to 120 mg/dL, HgA1C ≥6.5% or ongoing treatment with hypoglycemic medication.
• Willing to give written informed consent and able to understand, to participate in and to comply with the study requirements.

Exclusion Criteria:

• Women lactating or pregnant. All women with childbearing potential will undergo a urine pregnancy test at each visit to exclude pregnancy.
• Treatment with an investigational product within the last 30 days.
• Clinically evident major illness of other organ systems, including end-stage cancer, renal failure, or other conditions that in the opinion of the principal investigator make a clinical study inappropriate.
• Inability to provide informed consent.
• Clinical instability that would preclude withholding medications as determined by the study physician.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TUDCA Group; All subjects will receive 500 mg/day in a one week run-in period and then 1750 mg/day in one week treatment period of of the nutritional supplement Tauroursodeoxycholic acid (TUDCA).	Dietary supplement: Tauroursodeoxycholic acid; Tauroursodeoxycholic acid is an ambiphilic bile acid. It is the taurine conjugate form of ursodeoxycholic acid.; Other Names: TUDCA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in vascular function	Endothelium -dependent flow-mediated dilation of the brachial artery by ultrasound and fingertip tonometry at baseline and 5-minute cuff occlusion of the upper arm.	before and 4 hours after TUDCA treatment at the screening and 3 study visits during a 2 week period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in endoplasmic reticulum stress	Endothelial cells will be collected utilizing a J-wire inserted into an arm vein with an 18 gauge catheter using sterile technique and local anesthesia. ER stress will be measured by the study of early and chronic markers of ER stress activation by western blotting and PCR techniques.	before and 4 hours after TUDCA treatment at the screening and 3 study visits during a 2 week period
Change in endothelial function	Endothelial cells will be collected utilizing a J-wire inserted into an arm vein with an 18 gauge catheter using sterile technique and local anesthesia. Endothelial function will be measured by the study of endothelial nitric oxide synthase activation and nitric oxide production	before and 4 hours after TUDCA treatment at the screening and 3 study visits during a 2 week period
Change in fasting glucose	The blood sample will be processed to measure fasting glucose levels	before and 4 hours after TUDCA treatment at the screening and 3 study visits during a 2 week period
Change in insulin levels	The blood sample will be processed to measure insulin levels	before and 4 hours after TUDCA treatment at the screening and 3 study visits during a 2 week period
Change in lipid levels	The blood sample will be processed to measure lipids levels including total cholesterol, LDL, HDL and triglycerides	before and 4 hours after TUDCA treatment at the screening and 3 study visits during a 2 week period

Collaborators and Investigators

• Sponsor: Boston University
• Investigators: Principal Investigator: Naomi Hamburg, MD, Boston University Medical Campus

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2018
• Primary Completion (Actual): February 9, 2021
• Study Completion (Actual): February 9, 2021

Study Registration Dates

• First Submitted: February 27, 2018
• First Submitted That Met QC Criteria: March 9, 2018
• First Posted (Actual): March 13, 2018

Study Record Updates

• Last Update Posted (Actual): March 24, 2021
• Last Update Submitted That Met QC Criteria: March 20, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Endoplasmic Reticulum Stress; Tauroursodeoxycholic acid (TUDCA); Endothelial function in humans
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Anti-Infective Agents; Antiviral Agents; Gastrointestinal Agents; Cholagogues and Choleretics; Ursodoxicoltaurine
• Other Study ID Numbers: H-35009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No